Study of genetic diseases with neoplastic manifestations and detailed investigation of families at high risk of cancer may help detect environmental and genetic influences in carcinogenesis. Methods include review of prior medical and environmental history; documentation of history; collection and distribution of biological specimens; review of hospital records of patients with selected genetic diseases or neoplasms; and survey of childhood cancer death certificates in the U.S. since 1960. Report on multiple malignancies emphasized the co-existence of additional benign tumors in patients, as well as benign and malignant tumors in their families. Laboratory studies revealed subclinical immune defects in a family with EBV-related malignancies and a new syndrome of birth defects, and minor bony birth defects and bone marrow dysfunction in a family with osteosarcoma. A monograph, Genetics of Human Cancer, was edited and published. The same approach will be continued, using new laboratory methods and epidemiologic clues from other sources as available. BIBLIOGRAPHIC REFERENCES: Mulvihill, J.J.: Genetic repertory of human neoplasia. In Mulvihill, J.J., Miller, R.W. and Fraumeni, J.F., Jr. (eds.): Genetics of Human Cancer. New York, Raven Press, 1977, pp. 137-143. Mulvihill, J.J.: Host factors. In Harris, C. (ed.): Pathogenesis and Therapy of Lung Cancer. New York, Marcel Dekker, 1977, in press.